Treatment with oxiracetam or choline restores cholinergic biochemical and pharmacological activities in striata of decorticated rats.
Interruption of the corticostriatal pathway by undercutting the frontal cortex resulted after 2 weeks in a 40% reduction of basal acetylcholine (ACh) release in vivo, and in inhibition of the striatal sodium-dependent high-affinity uptake of choline (SDHACU) to the same extent. The lesion, too, completely prevented the rise (about 35%) in striatal ACh content induced by oxotremorine and apomorphine acting at muscarine and dopamine receptors, respectively. Acute intraperitoneal injections of 100 mg/kg of either oxiracetam or choline chloride resulted in time-dependent recovery of ACh output from the striata of decorticated rats to control levels. Oxiracetam also normalized the ex vivo striatal SDHACU activity of decorticated rats 2 h after administration without any effect in sham-operated rats. Oxiracetam or choline chloride administered before oxotremorine (0.8 mg/kg, i.p.) or apomorphine (1 mg/kg, i.p.) reinstated the ACh-increasing effect of these agonists. It is suggested that choline chloride acts directly simply by being the precursor for ACh, whereas oxiracetam may act indirectly, possibly by increasing the availability of choline chloride for ACh synthesis. Furthermore, the frontally decorticated rat could constitute a useful model for studying means to restore the deficit in striatal cholinergic neurotransmission.
Consolo
S
S
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Salmoiraghi
P
P
Amoroso
D
D
Kolasa
K
K
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism*; D003655:Decerebrate State; D005260:Female; D010095:Oxotremorine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011759:Pyrrolidines; D010095:Oxotremorine; D001058:Apomorphine; D002794:Choline; D000109:Acetylcholine; C040619:oxiracetam